DESCRIPTION: The applicant proposes to determine if augmentation of 7alpha-hydroxylase activity in the liver or ectopic expression of 7alpha-hydroxylase in macrophages has a favorable effect on atherogenesis in hyperlipidemic mice. The first aim is to determine how transgenic expression of 7alpha-hydroxylase in the liver of hyperlipidemic mice influences plasma lipoprotein levels and atherogenesis. The second aim is to determine if the transgenic expression of 7alpha-hydroxylase in macrophages of hyperlipidemic mice influences atherogenesis. In other studies, bone marrow of hyperlipidemic mice will be replaced with stem cells obtained from mice expressing a 7alpha-hydroxylase macrophage-specific transgene.